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Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control
The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated novel peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and prog...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974408/ https://www.ncbi.nlm.nih.gov/pubmed/23793098 http://dx.doi.org/10.1038/nm.3229 |
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author | Ranasinghe, Srinika Cutler, Sam Davis, Isaiah Lu, Richard Soghoian, Damien Z. Qi, Ying Sidney, John Kranias, Gregory Flanders, Michael Lindqvist, Madelene Kuhl, Bjorn Alter, Galit Deeks, Steven G. Walker, Bruce D. Gao, Xiaojiang Sette, Alessandro Carrington, Mary Streeck, Hendrik |
author_facet | Ranasinghe, Srinika Cutler, Sam Davis, Isaiah Lu, Richard Soghoian, Damien Z. Qi, Ying Sidney, John Kranias, Gregory Flanders, Michael Lindqvist, Madelene Kuhl, Bjorn Alter, Galit Deeks, Steven G. Walker, Bruce D. Gao, Xiaojiang Sette, Alessandro Carrington, Mary Streeck, Hendrik |
author_sort | Ranasinghe, Srinika |
collection | PubMed |
description | The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated novel peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors (n=1085). We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with DRB1*15:02 significantly associated with low viremia (P=0.003, q=0.04) and DRB1*03:01 significantly associated with high viremia (P=0.004, q=0.04). Interestingly, a sub-group of HLA-DRB1 alleles linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 alleles linked with high viremia (p=0.018). Our data provide systematic evidence that HLA-DRB1 allele expression significantly impacts the durable control of HIV replication, an effect that appears to be mediated primarily by the protein-specificity of HIV-specific CD4(+) T cell responses to Gag and Nef. |
format | Online Article Text |
id | pubmed-3974408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39744082014-04-03 Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control Ranasinghe, Srinika Cutler, Sam Davis, Isaiah Lu, Richard Soghoian, Damien Z. Qi, Ying Sidney, John Kranias, Gregory Flanders, Michael Lindqvist, Madelene Kuhl, Bjorn Alter, Galit Deeks, Steven G. Walker, Bruce D. Gao, Xiaojiang Sette, Alessandro Carrington, Mary Streeck, Hendrik Nat Med Article The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated novel peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors (n=1085). We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with DRB1*15:02 significantly associated with low viremia (P=0.003, q=0.04) and DRB1*03:01 significantly associated with high viremia (P=0.004, q=0.04). Interestingly, a sub-group of HLA-DRB1 alleles linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 alleles linked with high viremia (p=0.018). Our data provide systematic evidence that HLA-DRB1 allele expression significantly impacts the durable control of HIV replication, an effect that appears to be mediated primarily by the protein-specificity of HIV-specific CD4(+) T cell responses to Gag and Nef. 2013-06-23 2013-07 /pmc/articles/PMC3974408/ /pubmed/23793098 http://dx.doi.org/10.1038/nm.3229 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Ranasinghe, Srinika Cutler, Sam Davis, Isaiah Lu, Richard Soghoian, Damien Z. Qi, Ying Sidney, John Kranias, Gregory Flanders, Michael Lindqvist, Madelene Kuhl, Bjorn Alter, Galit Deeks, Steven G. Walker, Bruce D. Gao, Xiaojiang Sette, Alessandro Carrington, Mary Streeck, Hendrik Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control |
title | Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control |
title_full | Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control |
title_fullStr | Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control |
title_full_unstemmed | Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control |
title_short | Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control |
title_sort | association of hla-drb1-restricted cd4(+) t cell responses with hiv immune control |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974408/ https://www.ncbi.nlm.nih.gov/pubmed/23793098 http://dx.doi.org/10.1038/nm.3229 |
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